Acoustic cavitation is one of two mechanisms causing bioeffects in diagnostic ultrasound (heating is the other). Inertial cavitation is considered a main mechanism of kidney stone comminution in lithotripsy, has been shown to play a dominant role in ultrasound-accelerated fibrinolysis, and is important in transdermal drug delivery and ultrasonic gene transfection. However, most cavitation detection and quantification methods depend upon symmetrical (spherical) inertial collapse of a bubble. While symmetrical inertial cavitation (S-IC) may occur when a bubble is located many radii from other structures, in most biomedical applications bubbles are very close to vessel walls, blood cells, or solid surfaces. Under these circumstances, the bubble collapse may be asymmetrical, producing a liquid jet that can pit surfaces or open transient pores in cell membranes. There is currently no reliable method of quantifying asymmetrical inertial cavitation (AS-IC), or of measuring the effect of adjacent structures on microbubble dynamic response to ultrasound. The long-range objective of the project is to develop an ultrasonic detection technique to quantify AS-IC of microbubbles that are constrained by surrounding structures. Specific aims are 1) to use active cavitation detection (ACD) methods to investigate response of microbubbles inside a fibrin clot, 2) to wed long-pulse Doppler techniques with ACD to determine the "Doppler signature" of AS-IC in contrast to SIC, and 3) to use the Doppler signature of AS-IC to quantify asymmetrical cavitational activity in vitro. ACD uses a low-amplitude, high-frequency (e.g., 20-30 MHz) probe pulse to interrogate a bubble undergoing inertial cavitation in response to a biomedically-relevant ultrasonic pulse (e.g., 2 MPa pp, 5-cycle toneburst with 1 MHz center frequency). A technique to identify and quantify AS-IC of microbubbles in contact with cells and other surfaces will provide insight into the mechanisms of ultrasound bioeffects in diagnosis and improve understanding of ultrasound therapy.